Sundry mevalonate-derived constituents (isoprenoids) of fruits, vegetables and cereal grains suppress chemically-initiated carcinogenesis. This action has been attributed to the isoprenoid-mediated induction of detoxifying activities and to the antioxidant activity of some isoprenoids. Neither action explains the potent impact isoprenoids have on the promotion/progression stage of chemically-initiated carcinogenesis and on the growth of chemically established and implanted tumors (reviewed by Elson, 1995; Elson and Yu, 1994). Isoprenoids differ substantially in the impact they have on tumor growth. Isoprenoids suppress, via post-transcriptional actions (Correll, et al., 1994; Parker, et al., 1993; D. M. Peffley and A. K. Gayen, personal communication), 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, the activity deemed to be rate-limiting for the synthesis of cholesterol. The statins are competitive inhibitors of HMG-COA reductase. Correlations between the late stage tumor-suppressive potency of diverse isoprenoids and their impact on HMG-CoA reductase activity approach unity. The reductase activity of tumors differs from that of liver in being resistant to sterol feedback regulation. The tumor activity however retains high sensitivity to post-transcriptional regulation as triggered by diverse isoprenoids. As a consequence of the isoprenoid-mediated suppression of HMG-CoA reductase activity the pools of mevalonate pathway intermediates become limiting for the post-translational processing of growth-associated proteins (reviewed by Elson, 1995; Elson and Yu, 1994).
One recent review presented a list of structurally diverse isoprenoids with varying capacity to suppress mevalonate synthesis (Elson, 1995).